Aromatic esters of alphahydroxyisobutyric acids



Patented Dec. 7, 1943 Z EBfiBl? L NE? f QFFICE AROMATIC ESTERS F ALPHA- HYDROXYISOBUTYRIC ACIDS Jack T. Thurston, Cos Cob, and John M. Grim,

Stamford, Conn, assignors'to American Cyanamid Company, New York, N. Y., a corporation of Maine No Drawing. Application November 6, 1940, Serial 'No. 364,553

2 Claims. (Cl. 268-484) The present invention relates to a new class able to replace he hy n of he y yl of chemical compounds comprising the aromatic g up W t an y group p r to the production esters of pha-hydroxyisobutyric acid and the f th rydroxy substituted derivatives thereof. Any a matic a o l y e used f r l hese new compounds have a wid field of 5 ducing the esters in accordance with the present usefulness of considerable commercial imporinv nti n and in lud s b adly m d Xy tance in the arts. Many of the compounds areara kyl mp unds in whi h t e alkyl up m y slightly viscous liquids having relatively high either be saturated or unsaturated and also hyboiling points while others are solid substances. d Xy yl compounds Containing a plurality In general, the compounds ar wat r ins l bl of aryl radicals including compounds having subbut miscible with or solvents for organic comstituents on the aromatic rings. Among the pounds. Among the various use to which th more common aromatic alcohols that can be used compounds may be put are as solvents for lacare benzyl alcohol, phenylethyl alcohol, phenylquers, inks, and various coating compositions. p py a haphthylmethyl alcohol, p Many of the compounds are also useful as plas- 5 yl et y alcohol, pheny ethyl alcohol, cinticizers and modifiers for synthetic resins, nitronamyl alcohol, or any Su h Co p having cellulose. cellulose acetate, cellulose propionate, trohalogen. o i acidalkyl or other S cellulose others and similar compositions. The Stituoht up o the a c ringcompounds are also useful as intermediates in In the general formula when R represents an the preparation of methacrylates and as latent organic acyl radical the compounds usually have catalysts in the preparation of resins. a slightly higher boiling point, are more stable The invention includes broadly any of the aroand are better solvents for some of the nitromatic alcohol esters of alpha-hydroxyisobutyric cellulose and similar composition Among e acid as well as such esters when the hydrogen of ious acyl radicals that can be used to rep the ydroxyl group has been replaced by various the hydrogen of the hydroxyl group are the aliorganic radicals. The following general formula phatic acyl radicals such as formyl, a y 1 represents the compounds which are included in p nyl, buty yl, octanoyl, and ca bonic.

the present invention: The acyl radical may also be that of a cycloaliphatic acid such as cyclohexyl acetic acid,

[CH3 O.- -R camphoric acid and the like. The acyl radical 0 may likewise be an aromatic radical such as I OH those of benzoic acid or salicylic acid. Dicar- 3 boxylic acids may also be used to acylate the hyin which R may be hydrogen or an aliphati arodroxyl groups in which case two molecules of matlo, yo a phatic or heterocyclic radical alpha-hydroxyisobutyric acid are combined with Capable of replacing the hydrogen on he hyone molecule of the dicarboxylic acid, or the droxyl group, or an alkali metal, 12 is an integer mono-esters of the dicarboxylic acids may be and R 18 an a yl r di a employed in which case one molecule of alpha- The esters of the present invention y e hydroxyisobutyric acid will combine with one p pa ed y a y f the m th ds rdina y mmolecule of the mono-ester of the dicarboxylic pl y l in the production of esters and the invenacid. Among the various dicarboxylic acids and tloh is not intended to be limited y y p mono-esters which can be used are those such as ulor method r producing hem. We hav f nd succinic, oxalic, diglycolic, sebacic, maleic, na hthat the aromatic est s of D Y Y thalene dicarboxylic, phthalic, chlorophthalic, butyrlo and can he p p y r i y nitrophthalic, and the like. Ether-acids may suitable aromatic alcohol such as benzyl alcohol also b employed to produce acylated aromatic wi h phay r xyis tyri a id at elevated esters of alpha-hydroxyisobutyric acid in which temperatures in t e presence or absence of a case B in the general formula represents the catalyst such as sulfuric acid or toluene sulfonic 50 d 1 of n th r-acid such as:

acid. The esters may likewise be prepared by the B t ti acid ester interchange method or by reacting aralkyl A' halide such as benzyl chloride with an alkali CH" O-0HCH2 O CH CO0H (Beta-n-butoxy-etlloxy) acetic acid metal salt of alpha-hydroxyisobutyric acid. C4HP-OCHQCHQ-O CF?OH2O-CH2-OOOH When compounds are to be produced in whic (Beta'n'bumxy'dlethmy) am the hydrogen of the hydroxyl group is replaced r 6Hll-0CH2C0OH Oyclohexyloxyacetic acid by some other radical, it may be desirable in some Q th )b e 'a-nll OXY-G OXY 0112010 {101 lnstances to produce the aromatic ester first. and C.HQO QH, .CF2 O CHPCHZAFCHFCHPC09H then replace the hydrogen of the hydroxyl group (B a-n-but yo y) p oo c acid with an organic radical such as for example. on The'hydrogen of the hydroxyl group may also be acyl radical; and in other cases it may be desirreplaced by heterocyclic acids under certain conditions such as forexample the radical of nicotinic acid.

As pointed out heretofore the hydrogen on the hydroxyl group may be replaced by an acyl radical either prior to the production of the aromatic ester of alpha-hydroxyisobutyric acid or the ester may be prepared first and then the hydroxyl group acylated. In most cases the acid halides may be used to replace the hydrogen of the hydroxyl groups as for example, acetyl chloride may be used to produce alpha-acetylated esters or acids.

Ethers of the aromatic esters of alpha-hydroxyisobutyric acid are produced when the hydrogen of the hydroxyl group is replaced by either an alkyl, cycloaliphatic, aralkyl, or aryl group and such ether esters have properties difiering somewhat from the esters themselves. The alkyl radicals used to replace the hydrogen may be either saturated or unsaturated and may or may not contain substituent groups. Included in this group of alkyl radicals are the methyl, ethyl, propyl, butyl, isobutyl, octyl, as well as alkyl radicals containing carboxylic and oxy groups in the chain to produce compounds such as the following: (CH3)2C[O.CH2.CH(CH3)2].COOR1,

The hydrogen may also be replaced by alicyclic radicals such as cyclohexanyl, methyl, cyclohexanyl, etc.

The various aralkyl radicals may be also used to replace the hydrogen such as benzyl, phenethyl, phenylpropyl, naphthylmethyl, diphenylmethyl, diphenylethyl, cinnamyl, etc.

The hydrogen f the hydroxyl group may be replaced by any of the aliphatic or aromatic radicals mentioned above by reacting the sodium salt of the aromatic esters of alpha-hydroxyisobutyric acid with the desired aliphatic or aromatic halides or sulfates.

The hydrogen of the hydroxyl group of the arcmatic esters of alpha-hydroxyisobutyric acid may also be replaced by groups possessing ketones or aldehyde radicals. For example, halogenated ketones may be reacted with the sodium salt of the aromatic esters of alpha-hydroxyisobutyric acid to split off sodium halide and substitute the ketone radical in place of the hydrogen of the hydroxyl group. For example, when chloroacetone is reacted as described above the following compound is produced:

onacocrnoccoam 31592 The corresponding aromatic ketones may be used instead of acetone. When chlorinated aldehydes are employed the aldehyde radical replaces the hydrogen in the hydroxyl group.

The carbonic acid esters of the aromatic esters of alpha-hydroxyisobutyric acid can be prepared by reacting the aromatic ester with, for example, ethyl chloroformate to produce the alpha carboethoxy aromatic ester.

Various metal radicals may be used to replace the hydrogen of the hydroxyl group of the esters and particularly active metals such as the alkali metals, sodium and potassium. These salts are produced by adding sodium or potassium to the aromatic ester of alpha-hydroxyisobutyric acid in an inert solvent and refluxing. In some cases it is more desirable to prepare the sodium or potassium salts by reacting the aromatic ester of alpha-hYdroxyisobutyria acid with the metallic EXAMPLE 1 I-naphthylmethyl alpha-hydroxyisobutyrate Materials Grams l-(chloromethyl) naphthalene 58.8 Alpha-hydroxyisobutyric acid 16. 6 Potassium alpha-hydroxyisobutyric acid 47. 3

This reaction mixture was heated for about one hour at -160 C. in a round-bottomed flask fitted with a stirrer. The temperature was then raised to l70-180 C. and the heating was continued for three hours more. The whole mass was treated with 200 cc, of water, neutralized with sodium hydroxide and then extracted with carbon tetrachloride and dried. After the carbon tetrachloride had been distilled the dark oily liquid remaining was dissolved in naphtha and decolorized with activated charcoal. On cooling 2. yellow oily layer separated, which crystallized when cooled in an ice-salt bath. The solid was distilled at 128-133 C. at about 1 mm. pressure, yielding 53 grams or 65% of the theoretical yield of a viscous and light straw-colored product which crystallized on standing overnight. After recrystallization from heptane the alpha-naphthylmethyl alpha-hydroxyisobutyrate melted at 50-52 C. and had a saponification number of 226.8.

EXAMPLE 2 Benzyl alpha-hydroxyisobutyrate These materials were refluxed together in a round-bottomed flask fitted with a 12-inch Vigreaux column and a distillation head which controlled the ratio of reflux to draw-01f. The bath temperature was kept at 210 C. to 220 C. for three hours. During this time 54 grams of water was removed. The residue was diluted with carbon tetrachloride, neutralized with sodium bicar bonate and washed With water. After drying on anhydrous sodium sulfate the carbon tetrachloride solution was fractionated at reduced pressure yielding 418 grams or 72% of the theoretical yield of benzyl alphahydroxyisobutyrate distilling at 104l08 C./3 mm. The saponification number was found to be about 233.

EXAMPLE 3 Diphenylmcthyl alp-ha-hydroxyisobutyrate Materials Grains Benzhydrol (diphenylmcthyl alcohol). Alpha-hydroxyisobutyrie acid Xylene The residue was neutralized with sodium bicarbonate, washed with water, extracted with benzene and dried. After the benzene was removed by distillation the diphenylmethyl alphahydroxyisobutyrate crystallized on cooling. It was recrystallized from naphtha giving 26 grams or 45% of the theoretical yield of a white crystalline product melting at 6l-62 C. and possessing a saponification number of about 213.

EXAMPLE 4 Z-phenethyl alpha-hydromyisobutymte Materials Grams 2-phenylethyl alcohol Alpha-hydroxyisobutyric acid p-toluenesulionlc acid EXAMPLE 5 Cinnamyl alpha-hydroxyisobutyrate Materials Grams Cinnamyl alcohol Alpha-hydroxyisobutyric acid This reaction mixture was heated under reflux at 180 C. for three hours, during which time 9 cc. of water was removed. After neutralizing the carbon tetrachloride solution with sodium bicarbonate, washing several times with water, it was dried on anhydrous sodium sulfate. It was then fractionated at reduced pressure and gave 28 grams or 25% of the theoretical yield of cinnamyl alpha-hydroxyisobutyric acid ester, which distilled at l12117 C. at less than 1 mm. pressure and possessed a saponification number of about 256.

EXAMPLE 6 Alpha-carboethoxyisobutyrate When ethyl chlorocarbonate (1 mol) is slowly added to a toluene solution of the benzyl ester of alpha-hydroxyisobutyric acid (1 mol) and pyridine (1 mol) at room temperature pyridine hydrochloride is precipitated and the alphacarboethoxy derivative of the ester is obtained as illustrated by the following equation:

This ester is difiicult to distill since it decomposes to yield benzyl methacrylate.

EXAMPLE 7 Acetylated benzyl ester of aZpha-hydromyz'sobutyric acid When equivalent molecular weights of the benzyl ester of alpha-hydroxyisobutyric acid and acetyl chloride are refluxed for about six hours, and then distilled at reduced pressure the acetylated ester is obtained as illustrated by the following equation:

Using a procedure similar to that above, a good yield of the acetyl derivative of benzyl alphahydroxyisobutyrate boiling at -115 C. 1-2 mm. was obtained.

EXAMPLE 8 Benzyl alpha-capryloxyisobutyrate Equimolar quantities of the benzyl ester of alpha-hydroxyisobutyric acid and capric acid, protected by an atmosphere of nitrogen, were heated at 160-220 C. for 70 hours, during which time the acid number of the reaction decreased from to 9. The product was purified by distillation, yielding a colorless mobile liquid, boiling at C./l min. and having a saponification number of 161.

EXAMPLE 9 Alpha-naphthylmethyZ-alpha-benzoylomyisobutg mte i Equimolar quantities of alpha-naphthylmethylisobutyrate (Example 1) and benzoyl chloride were mixed together in an excess of pyridine and allowed to stand overnight. This reaction mixture was then heated on a steam bath for about three hours, cooled to room temperature and poured into an excess of cold, dilute hydrochloric acid. The product was extracted with carbon tetrachloride, washed several time with water, dried, and freed of the solvent. The viscous residue which was allowed to stand at room temperature slowly crystallized. The crystalline product which was dissolved in hot naphtha, decolorized with charcoal and recrystallized once more, melted at 76-77 C.

EXAMPLE 10 Benzyl alpha-ethoxyisobwtyrate The benzyl alpha-sodiuinoxyisobutyrate was prepared by adding an equivalent of sodium metal to the ester dissolved in benzene and heating on a steam bath until the sodium dissolved. To this solution, cooled in an ice bath, was added a slight excess of diethyl sulfate while keeping the temperature below 15 C. The reaction mixture was then heated at about 85 for three hours. After washing with water and drying on anhydrous We claim: sodium sulfate, the excess benzene wa removed, Compounds a ng t e o owing general and the product distilled at reduced pressure. formula! OH OH EXAMPLE 11 C 01 18 c o R1 B enzyz alphabenzyzoxwsobutymte in which R1 is a member of the group consisting of aralkyl and aralkylene radicals. Equlmolar quantities of benzyl alpha-sodium- The compound having the formula: oxyisobutyrate and benzyl chloride in xylene were refluxed for four hours, then washed with water, 7 OH: OH

dried and distilled. A yield g.) of the water-white mobile product distilling at C./5 01120035 mm. was obtained. It had a saponification num- 5 JACK T. THURSTON.

ber of 190. JOHN M. GRIM. 

